This proposal for a Specialized Program of Research Excellence (SPORE) in Breast Cancer at The Johns Hopkins Medical Institutions brings together a highly interactive, multi-disciplinary program of translational research in breast cancer. The SPORE includes four research programs with seven integrated projects spanning the fields of risk assessment, diagnosis, staging, treatment, and prevention. Program 1, Development of molecular markers to define breast cancer progression and classification. Project 1A, Molecular markers for breast cancer (Saraswati Sukumar Ph.D.), Project 1B, Molecular phenotypes of breast cancer (Edward Gabrielson M.D.). Program 2 Project 2A, Molecular detection of breast cancer (James Herman M.D.). Program 3, Development of molecular strategies for breast cancer therapy and prevention. Project 3A, Novel polyamine analogs for breast cancer treatment (Robert Casero Ph.D.); Project 3B, Use of demethylating and histone deacetylating agents to treat breast cancer (Nancy Davidson agents to treat breast cancer (Nancy Davidson, M.D.); Project 3C, Vaccines: A new paradigm for breast cancer prevention (Elizabeth Jaffee, M.D.). Program 4 Project 4A, Molecular epidemiology of progression to breast cancer (Kathy Helzlsour M.D., MHC). These seven research projects are supported by three cores: Core 1, Administration and communications (Nancy Davidson, M.D.). Core 2, Human specimen resource and database (Mark Sherman M.D.) To facilitate career development of individuals with an interest in translational breast cancer research.